Language

English

Publication Date

8-26-2025

Journal

Blood Advances

DOI

10.1182/bloodadvances.2024015779

PMID

40334068

PMCID

PMC12359224

PubMedCentral® Posted Date

5-9-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) with central nervous system (CNS) involvement (CNS B-ALL) have poor outcomes and were frequently excluded from CD19-targeting chimeric antigen receptor (CAR) T-cell clinical trials. The efficacy and safety of brexucabtagene autoleucel (brexu-cel) in adults with R/R B-ALL was established by the ZUMA-3 trial, which excluded patients with advanced or symptomatic CNS involvement. In this retrospective multicenter analysis, we investigated the safety and efficacy of brexu-cel in patients with CNS B-ALL using data from the ROCCA (Real-World Outcomes Collaborative for CAR T in ALL) consortium. Of 189 patients who received infusion, 31 had CNS-2 (presence of blasts in cerebrospinal fluid with < 5 white blood cells [WBCs] per μL) or CNS-3 (presence of blasts with >5 WBCs per μL and/or clinical signs/symptoms) disease before apheresis and are the focus of this report. The median age was 46.5 years (range, 24-76), and 58.1% were male. Most (87.1%) received bridging therapy. After brexu-cel, 21 of 24 patients with CNS restaging (87.5%) achieved CNS-1. Additionally, 28 of 30 evaluable patients achieved marrow complete remission; 25 were measurable residual disease negative. No statistically significant differences were seen in progression-free survival or overall survival after brexu-cel among patients with or without CNS involvement. Similarly, grade 3/4 immune effector cell-associated neurotoxicity syndrome occurred similarly in patients with (35.5%) and without (30%) CNS disease. In conclusion, our data suggest that brexu-cel results in high response rates in patients with CNS B-ALL, with toxicity comparable with that in patients without CNS involvement.

Keywords

Humans, Male, Female, Adult, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Middle Aged, Central Nervous System Neoplasms, Immunotherapy, Adoptive, Treatment Outcome, Retrospective Studies, Young Adult, Aged, Recurrence, Receptors, Chimeric Antigen

Published Open-Access

yes

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